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2. Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus

Author

Lopes, VS, Boye, SE, Louie, CM, Boye, S, Dyka, F, Chiodo, V, Fofo, H, Hauswirth, WW, and Williams, DS

Subjects
Eye Disease and Disorders of Vision, Biotechnology, Neurosciences, Gene Therapy, Genetics, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Eye, Animals, DNA, Complementary, Dependovirus, Gene Expression, Gene Transfer Techniques, Genetic Therapy, Green Fluorescent Proteins, Humans, Mice, Myosin VIIa, Myosins, Retina, Retinal Degeneration, Usher Syndromes, Usher syndrome, gene therapy, adeno-associated virus, retina, RPE, MYO7A, Biological Sciences, Medical and Health Sciences
Abstract

Usher 1 patients are born profoundly deaf and then develop retinal degeneration. Thus they are readily identified before the onset of retinal degeneration, making gene therapy a viable strategy to prevent their blindness. Here, we have investigated the use of adeno-associated viruses (AAVs) for the delivery of the Usher 1B gene, MYO7A, to retinal cells in cell culture and in Myo7a-null mice. MYO7A cDNA, under control of a smCBA promoter, was packaged in single AAV2 and AAV5 vectors and as two overlapping halves in dual AAV2 vectors. The 7.9-kb smCBA-MYO7A exceeds the capacity of an AAV vector; packaging of such oversized constructs into single AAV vectors may involve fragmentation of the gene. Nevertheless, the AAV2 and AAV5 single vector preparations successfully transduced photoreceptor and retinal pigment epithelium cells, resulting in functional, full-length MYO7A protein and correction of mutant phenotypes, suggesting successful homologous recombination of gene fragments. With discrete, conventional-sized dual AAV2 vectors, full-length MYO7A was detected, but the level of protein expression was variable, and only a minority of cells showed phenotype correction. Our results show that MYO7A therapy with AAV2 or AAV5 single vectors is efficacious; however, the dual AAV2 approach proved to be less effective.

Published
2013

21. Dealing with fuel contaminants in biogas-fed solid oxide fuel cell (SOFC) and molten carbonate fuel cell (MCFC) plants : Degradation of catalytic and electro-catalytic active surfaces and related gas purification methods

Author

Lanzini, A., Madi, H., Chiodo, V., Papurello, D., Maisano, S., Santarelli, Massimo, Van herle, J., Lanzini, A., Madi, H., Chiodo, V., Papurello, D., Maisano, S., Santarelli, Massimo, and Van herle, J.

Abstract

Fuel cell and hydrogen technologies are re-gaining momentum in a number of sectors including industrial, tertiary and residential ones. Integrated biogas fuel cell plants in wastewater treatment plants and other bioenergy recovery plants are nowadays on the verge of becoming a clear opportunity for the market entry of high-temperature fuel cells in distributed generation (power production from a few kW to the MW scale). High-temperature fuel cell technologies like molten carbonate fuel cells (MCFCs) and solid oxide fuel cells (SOFCs) are especially fit to operate with carbon fuels due to their (direct or indirect) internal reforming capability. Especially, systems based on SOFC technology show the highest conversion efficiency of gaseous carbon fuels (e.g., natural gas, digester gas, and biomass-derived syngas) into electricity when compared to engines or gas turbines. Also, lower CO2 emissions and ultra-low emissions of atmospheric contaminants (SOX, CO, VOC, especially NOX) are generated per unit of electricity output. Nonetheless, stringent requirements apply regarding fuel purity. The presence of contaminants within the anode fuel stream, even at trace levels (sometimes ppb levels) can reduce the lifetime of key components like the fuel cell stack and reformer. In this work, we review the complex matrix (typology and amount) of different contaminants that is found in different biogas types (anaerobic digestion gas and landfill gas). We analyze the impact of contaminants on the fuel reformer and the SOFC stack to identify the threshold limits of the fuel cell system towards specific contaminants. Finally, technological solutions and related adsorbent materials to remove contaminants in a dedicated clean-up unit upstream of the fuel cell plant are also reviewed., QC 20170620

Published
2017
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22. Valorization of Dry Orange Peel Residues by Gasification Process

Author

Chiodo, V., Maisano, S., Zafarana, G., Urbani, F., Antonio Galvagno, Prestipino, M., and Freni, S.

Subjects
Product gas, Gasification, Syngas, Residues, Product gas, Organic waste, Residues, Biomass, Syngas, Organic waste, Gasification
Abstract

The growing need to reduce the environmental impact of the modern lifestyle imposes a continuous development of novel technologies aimed at a severe reduction of pollutant emissions in order to ensure a tolerable quality of life in metropolitan areas. Among potential alternatives, particular attention has been recently addressed toward the exploitation of residual biomass and wastes as sources for syngas production by thermo-chemical processes for heat and power production. Fruits processing industries generate important amount of residues, which must be managed properly by recycling, incineration or land filling. Due to the high carbon content, these residues represent a significant source of energy that could be valorized by gasification processes. Hence, our attention was focused on the energy recovery from orange peels residues produced by a Sicilian agro-industrial company by steam gasification. Thermodynamic and experimental analysis were carried out. Experiments were performed in a fixed bed laboratory scale reactor working with catalytic materials (Ni/Al2O3, MgO and dolomite mineral) with the biomass in order to investigate the influence of experimental conditions on the outlet stream compositions, mainly in terms of hydrogen content of the produced syngas. Results were compared to thermodynamic data in order to gain information of the experimental method used. The results have confirmed successfully the experimental results compared with the simulation data. The highest concentration (65.9%) of hydrogen volume in the syngas mixture was reached with dolomite mineral as catalyst., Proceedings of the 24th European Biomass Conference and Exhibition, 6-9 June 2016, Amsterdam, The Netherlands, pp. 918-921

Published
2016
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35. Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3-/-/Nrl-/- mice, an all-cone model of CNGA3 achromatopsia

Author

Du, W., primary, Tao, Y., additional, Deng, W.-T., additional, Zhu, P., additional, Li, J., additional, Dai, X., additional, Zhang, Y., additional, Shi, W., additional, Liu, X., additional, Chiodo, V. A., additional, Ding, X.-Q., additional, Zhao, C., additional, Michalakis, S., additional, Biel, M., additional, Zhang, Z., additional, Qu, J., additional, Hauswirth, W. W., additional, and Pang, J.-j., additional

Published
2015
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